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Reliable biological communication with realistic constraints.

Communication in biological systems must deal with noise and metabolic or temporal constraints. We include these constraints into information theory to obtain the distributions of signal usage corresponding to a maximal rate of information transfer given any noise structure and any constraints. Generalized versions of the Boltzmann, Gaussian, or Poisson distributions are obtained for linear, quadratic and temporal constraints, respectively. These distributions are shown to imply that biological transformations must dedicate a larger output range to the more probable inputs and less to the outputs with higher noise and higher participation in the constraint. To show the general theory of reliable communication at work, we apply these results to biochemical and neuronal signaling. Noncooperative enzyme kinetics is shown to be suited for transfer of a high signal quality when the input distribution has a maximum at low concentrations while cooperative kinetics for near-Gaussian input statistics. Neuronal codes based on spike rates, spike times or bursts have to balance signal quality and cost-efficiency and at the network level imply sparseness and uncorrelation within the limits of noise, cost, and processing operations.

Action Potentials↗

Genetic consequences of polygyny and social structure in an Indian fruit bat, Cynopterus sphinx. II. Variance in male mating success and effective population size.

Variance in reproductive success is a primary determinant of genetically effective population size (Ne), and thus has important implications for the role of genetic drift in the evolutionary dynamics of animal taxa characterized by polygynous mating systems. Here we report the results of a study designed to test the hypothesis that polygynous mating results in significantly reduced Ne in an age-structured population. This hypothesis was tested in a natural population of a harem-forming fruit bat, Cynopterus sphinx (Chiroptera: Pteropodidae), in western India. The influence of the mating system on the ratio of variance Ne to adult census number (N) was assessed using a mathematical model designed for age-structured populations that incorporated demographic and genetic data. Male mating success was assessed by means of direct and indirect paternity analysis using 10-locus microsatellite genotypes of adults and progeny from two consecutive breeding periods (n = 431 individually marked bats). Combined results from both analyses were used to infer the effective number of male parents in each breeding period. The relative proportion of successfully reproducing males and the size distribution of paternal sibships comprising each offspring cohort revealed an extremely high within-season variance in male mating success (up to 9.2 times higher than Poisson expectation). The resultant estimate of Ne/N for the C. sphinx study population was 0.42. As a result of polygynous mating, the predicted rate of drift (1/2Ne per generation) was 17.6% higher than expected from a Poisson distribution of male mating success. However, the estimated Ne/N was well within the 0.25-0.75 range expected for age-structured populations under normal demographic conditions. The life-history schedule of C. sphinx is characterized by a disproportionately short sexual maturation period scaled to adult life span. Consequently, the influence of polygynous mating on Ne/N is mitigated by the extensive overlap of generations. In C. sphinx, turnover of breeding males between seasons ensures a broader sampling of the adult male gamete pool than expected from the variance in mating success within a single breeding period.

Animals↗

Cryptic striations in the upper mantle revealed by hafnium isotopes in southeast Indian ridge basalts.

The Earth's mantle is isotopically heterogeneous on length scales ranging from centimetres to more than 10(4) kilometres. This heterogeneity originates from partial melt extraction and plate tectonic recycling, whereas stirring during mantle convection tends to reduce it. Here we show that mid-ocean ridge basalts from 2,000 km along the southeast Indian ridge (SEIR) display a bimodal hafnium isotopic distribution. This bimodality reveals the presence of ancient compositional striations (streaks) in the Indian Ocean upper mantle. The number density of the streaks is described by a Poisson distribution, with an average thickness of approximately 40 km. Such a distribution is anticipated for a well-stirred upper mantle, in which heterogeneity is continually introduced by plate tectonic recycling, and redistributed by viscous stretching and convective refolding.

Journal Article↗

Quantitative analysis of sex differences in hormone accumulation in the zebra finch brain: methodological and theoretical issues.

The autoradiographic method was used to compare the numbers of hormone accumulating cells in several brain regions in male and female zebra finches (Poephila guttata) after injection of tritiated testosterone. The brain regions examined were the caudal nucleus of the hyperstriatum ventrale (HVc), magnocellular nucleus of the anterior neostriatum (MAN), robust nucleus of the archistriatum (RA), nucleus intercollicularis of the midbrain (ICo), the tracheosyringeal hypoglossal motor nucleus (nXIIts), and periventricular magnocellular nucleus of the anterior hypothalamus (PVM). All but the last of these regions are thought to be involved in the control of vocalizations in passerine song birds. Males have significantly more labelled cells in HVc and MAN. In RA, there is no difference in total percentage of labelled cells, but there is a sex difference in size distribution of labelled cells. No sex difference was detected in other brain regions. These differences are found when using a criterion for cell labelling which is based on the Poisson distribution, and the relative merits are evaluated of various quantitative criteria used in the analysis of steroid autoradiograms. The magnitude of the observed sex difference may be influenced by several biasing factors, yet the sex difference persists when corrections are applied to eliminate the biases, indicating that the sex difference is not an artifact of autoradiographic procedure. The magnitude of the sex difference in hormone accumulation has certain implications for the process of sexual differentiation of the brain.

Animals↗

A theoretical analysis of hemodynamic and biomechanical alterations in intracranial AVMs after radiosurgery.

PURPOSE: Stereotactic radiosurgery is being increasingly used to treat intracranial arteriovenous malformations (AVMs). However, successful radiosurgery may involve latent periods of 1-2 years prior to AVM obliteration. This latent period include states of altered flow patterns that may or may not influence hemorrhage probabilities. The probability of hemorrhage is likely to be related to the degree of biomechanical stress across the AVM shunt walls. This paper describes a theoretical analysis of the altered hemodynamics and biomechanical stresses within AVM shunts post-radiosurgery. METHODS AND MATERIALS: The mathematical model is comprised of linked flow compartments that represent the AVM and adjacent normal vasculature. As obliteration of the irradiated shunts occur, changes in flow rates and pressure gradients are calculated based on first order fluid dynamics. Stress on the AVM shunt walls is calculated based on tangential forces due to intramural pressure. Two basic models are presented: a distribution of shunts with fixed thin walls subject to step-function obliteration (Model I), and a distribution of shunts subject to luminal obliteration from slowly thickening walls (Model II). Variations on these models are analyzed, including sequential, selective and random shunt obliteration, and uniform or Poisson distributions of shunt radii. RESULTS: Model I reveals that the range of pressure alterations in the radiosurgically-treated AVM include the possibility of transient increases in the total biomechanical stress within the shunt walls prior to obliteration. Model II demonstrates that uniform luminal narrowing via thickened walls should lead to reduced transmural stresses. The precise temporal pattern of AVM flow decrease and biomechanical stress reduction depends on the selection of shunts that are obliterated. CONCLUSION: (a) The hemodynamic and biomechanical changes appear to be relatively independent of the shunt distribution but highly dependent on the temporal pattern of the obliterative process, (b) uniformly thickened shunt walls should uniformly decrease biomechanical stresses in the latent period prior to complete obliteration, but if uniform obliteration is not achieved, (c) transient alterations in pressure versus stress relationships may lead to temporarily increased biomechanical stress prior to complete obliteration, and (d) reduction in stress may not reach significant levels until the AVM is almost completely obliterated.

Arteriovenous Shunt, Surgical↗

Induction and distribution of damage in CHO-K1 and the X-ray-sensitive hamster cell line xrs5, measured by the cytochalasin-B-cytokinesis block micronucleus assay.

The micronucleus assay holds promise as a method for determining clastogenic effects of particular agents and for examining relative sensitivities of eukaryotic cells to such clastogens. In the following work, a detailed examination of the induction of micronuclei in radio-resistant Chinese hamster ovary fibroblasts (CHO-K1) and the DNA double-strand break repair-defective daughter cell line, xrs5, was performed. Cells were exposed to gamma-irradiation, bleomycin, etoposide, camptothecin and the restriction endonuclease PvuII. By a simplified statistical analysis of data, information on the expression of chromosomal damage, the distribution of damage and the role of cell cycle effects on damage expression was obtained from a relatively small number of cells. All 5 clastogens resulted in elevated levels of micronuclei in xrs5 compared to CHO-K1. An analysis of the distribution of micronuclei within treated populations revealed differences between the modes of damage. Significant deviation from the expected values indicated that expression of micronuclei does not follow an expected Poisson distribution. The frequencies of binucleated cells indicated micronucleus frequencies do not always correlate with inhibition of cell cycle progression. This work also demonstrates that caution is required in the interpretation of data obtained through micronucleus assays. In particular, it does not appear possible to proscribe simple numerical values of relative sensitivity or clastogenicity based on the relative number of micronuclei induced alone.

Animals↗

Visible evidence for differences in synaptic effectiveness with activity-dependent vesicular uptake and release of FM1-43.

Activity-dependent uptake and release of the fluorescent probe FM1-43 were used to compare synaptic performance (rates of transmitter release and synaptic vesicle turnover) at different frequencies in phasic and tonic motor neurons innervating the crayfish leg extensor muscle and in the tonic motor neuron of the opener muscle. The phasic extensor motor neuron, which has a high quantal content of transmitter release, accumulated and released FM1-43 more rapidly than the tonic motor neuron, especially at low frequencies of stimulation. Individual bright spots appeared on the varicosities of the junctional terminals during stimulation in FM1-43; these spots corresponded to zones of immunostaining for the synaptic vesicle associated protein synaptotagmin, but they were larger and less numerous than synapses identified by electron microscopy and appear to represent one to several synapses with their associated clusters of synaptic vesicles. The number of bright spots observed on varicosities of the tonic terminal after stimulation at >/=20 Hz is generally similar to values for responding units (n) calculated from binomial distributions derived from quantal analysis. At frequencies of </=10 Hz, bright spots did not usually appear on tonic extensor varicosities, and the quantal release patterns were best fitted with Poisson distributions. Another tonic motor neuron, the excitor of the opener muscle, showed individual bright spots at lower frequencies of stimulation, consistent with its higher quantal output at these frequencies and corresponding with the binomial fits for quantal release distributions. In this axon, the number of distinctive bright spots increased with frequency in the 2- to 20-Hz range, indicating increased participation of synapses during frequency facilitation. In the tonic extensor neuron terminals, the brightness and the size of the individual spots increased with frequency, and new foci of dye uptake appeared at the edges of preexisting spots. Relative intensity change varied considerably among individual spots during dye loading at different frequencies. Similarly, individual spots on a single tonic terminal destained at different rates when stimulated after previous loading with FM1-43. These results suggest differential performance of individual synapses or small groups of synapses, some being more effective in transmitter release than others, as inferred from previous ultrastructural and quantal analysis studies. The large overall differences between phasic and tonic synapses suggest differential regulation of transmitter release at individual synapses in the two neurons.

Animals↗

Effective size of nonrandom mating populations.

Nonrandom mating whereby parents are related is expected to cause a reduction in effective population size because their gene frequencies are correlated and this will increase the genetic drift. The published equation for the variance effective size, Ne, which includes the possibility of nonrandom mating, does not take into account such a correlation, however. Further, previous equations to predict effective sizes in populations with partial sib mating are shown to be different, but also incorrect. In this paper, a corrected form of these equations is derived and checked by stochastic simulation. For the case of stable census number, N, and equal progeny distributions for each sex, the equation is [formula: see text], where Sk2 is the variance of family size and alpha is the departure from Hardy-Weinberg proportions. For a Poisson distribution of family size (Sk2 = 2), it reduces to Ne = N/(1 + alpha), as when inbreeding is due to selfing. When nonrandom mating occurs because there is a specified system of partial inbreeding every generation, alpha can be substituted by Wright's FIS statistic, to give the effective size as a function of the proportion of inbred mates.

Breeding↗

Spatial and temporal analysis of the distribution of hantavirus pulmonary syndrome in Buenos Aires Province, and its relation to rodent distribution, agricultural and demographic variables.

We studied the spatial and temporal distribution of Hantavirus Pulmonary Syndrome (HPS) cases from 1998 to 2001 in the Buenos Aires Province, Argentina. HPS is a severe viral disease whose natural reservoir are rodents of the subfamily Sigmodontinae (Muridae) and which occurs in many countries of South and North America. We considered two spatial arrangements: cells of 18.5 x 18.5 km(2); and departments, the political subdivisions of the province, as spatial units. We tested the departure from a Poisson distribution of the number of cases per cell and per month with the Variance/Mean index, while the interaction between spatial and temporal clustering was tested by means of the Knox and Mantel tests. We constructed probability maps in which the HPS rates per department were considered Poisson variates according to population, area and the product of population and area. We analysed the relation between rodent distribution, environmental and demographic variables and HPS cases conducting preliminary univariate analysis from which we selected variables to enter in general linearized models. We found that both the spatial and temporal distribution of cases is strongly aggregated. The spatiotemporal interaction appears to be related to a strong seasonality and the existence of particular ecological conditions rather than epidemic transmission of the disease. The main explanatory variables for the distribution of HPS cases among the departments of the Buenos Aires Province were human population, the distribution of the rodent Oxymycterus rufus and evapotranspiration. The last two variables are probably indicators of favourable ecological conditions for the reservoirs, which encompass other variables not taken into account in this study.

Agriculture↗

Proficiency testing of water microbiology laboratories in The Netherlands.

In a 3-year period, four series of simulated water samples containing selected test strains were distributed to more than 50 laboratories in The Netherlands for bacteriological testing. Participating laboratories examined the samples by enrichment or membrane filtration methods, or both, for total coliform organisms, thermotolerant coliform organisms, faecal streptococci and standard plate counts (37 degrees and 22 degrees C) according to Dutch standard methods. The results were quantitatively satisfactory: the distribution of positive and negative results with subsamples conformed to stochastic variation; the standard deviation of membrane or plate counts was usually in the range which may be expected from a Poisson distribution, and there was good correspondence between average counts in participating laboratories and those expected from controls in the organizing laboratory. Problems of a qualitative nature were frequently encountered, however. Among them were a false positive response with a strain of Enterobacter cloacae in the thermotolerant coliform test; a false positive result with Clostridium perfringens in enrichment tests for total or thermotolerant coliform organisms and false positive results with Micrococcus varians in the faecal streptococcus test by membrane filtration. It is concluded that quality assessment should be a consistent activity in water microbiology laboratories. For this purpose, stable and well characterized reference materials are needed.

Bacteria↗

[Distribution of atomic density in protein globules].

The distribution of atomic density in the elastase and subtilysin globulas was modeled on the basis of their x-ray atomic coordinates and was consequently investigated through comparison with the normal Poisson distribution, using the chi2-test. The results from the above procedure are discussed in connection with the concept of kinetic constraints on the globula folding process as well as with the enzyme-machine hypothesis. It is shown that the minimum average dimensions of atomic irregularities in the protein globula are about 200 A3.

Pancreatic Elastase↗

Transients of perforin pore formation observed by fluorescence microscopic single channel recording.

A new type of single channel recording is described. Large pores were generated in the membranes of resealed human erythrocyte ghosts by incubation with perforin (cytolysin). The flux of the polar fluorescent probe Lucifer Yellow was measured in single ghosts by the fluorescence microphotolysis (photobleaching) technique. The distribution of flux rates for ghosts treated with a limiting perforin concentration showed equidistantly spaced peaks suggesting that subpopulations of ghosts with 0, 1 and 2 pores were resolved. Furthermore, distributions obtained for very different perforin concentrations could be well simulated by using one common value for the flux rate of the single pore (k = 4.65 x 10(-3) s) and assuming a Poisson distribution of pores among ghosts. The flux rate of the single pore corresponds to a pore radius of approximately 50 A, a value which is much smaller than that obtained previously by electron microscopic studies but which agrees well with recent electrical single channel recordings. Mature perforin pores were observed to be very stable. No closing events were detected at a time resolution of 0.2 s for a wide range of temperatures and Ca2+ concentrations. However, the formation of new pores was an unexpectedly slow process. Fluorescence microscopic single channel recording as introduced by this study is applicable to a variety of cellular systems and fluorescent probes and thus may complement the information obtainable by electrical single channel recording of anorganic ion fluxes.

Erythrocyte Membrane↗

Using observed load distributions with a simple model to analyse the epidemiology of sea lice (Lepeophtheirus salmonis) on sea trout (Salmo trutta).

Sea lice are ectoparasites of salmonids that have been associated with the recent decline in sea trout numbers in north-west Europe. Observed patterns of louse load distribution between sea trout in the seas surrounding the UK, Ireland and Norway and a simple model have been used to analyse the epidemiology of lice. Loads are aggregated and deviate strongly from the Poisson distribution, although less than is observed with many other parasites. The louse numbers on fish from offshore sites are slightly less variable than for fish from coastal sites with comparable mean loads. Analysis of louse development stages and sexes shows that selection between hosts by sea lice plays a limited role. If host selection is absent, then associated poor condition would be caused by, not the cause of, high louse burdens; however the absence of such selection is not proved. Scenarios with infection that is patchy in space and time best generate the aggregated load patterns observed; these patches accord with observed swarms of copepodids. Prevalence patterns may indicate the movement of trout between environments. Control of copepodids in infection 'hot spots', either directly or through control of louse egg production in their catchment, may reduce louse loads on wild sea trout and, in particular, extreme and damaging loads.

Animals↗

Theoretical maximal precision for mass-to-charge ratio, amplitude, and width measurements in ion-counting mass analyzers

A theory previously developed for spectra with detector-limited (i.e., signal-independent) Gaussian-distributed noise is applied to calculate the maximal precision with which mass spectral peak parameters (mass-to-charge ratio, amplitude, width) can be determined from a discrete spectrum with source-limited Poisson-distributed noise. The precision depends in a calculable way upon the peak shape, signal-to-noise ratio, and number of data points per peak width. Those dependencies are tested by analysis of simulated data. The theory provides estimates for the precision of a repeated experiment, based on data from a single discrete mass spectrum whose parameters are extracted by a least-squares fit to a specified line shape. The relevance of the predictions to present and potential time-of-flight performance is discussed.

Journal Article↗

Estimating the ascertainment probability from the number of ascertainments per proband.

Several methods of estimating the ascertainment probability from the distribution of the number of ascertainments per proband have been presented in the literature. Here these methods are compared. The Skellam often gives the best fit, but there are counter examples. The estimate from a Poisson distribution is generally close to the best solution.

Female↗

Binomial distribution based tau-leap accelerated stochastic simulation.

Recently, Gillespie introduced the tau-leap approximate, accelerated stochastic Monte Carlo method for well-mixed reacting systems [J. Chem. Phys. 115, 1716 (2001)]. In each time increment of that method, one executes a number of reaction events, selected randomly from a Poisson distribution, to enable simulation of long times. Here we introduce a binomial distribution tau-leap algorithm (abbreviated as BD-tau method). This method combines the bounded nature of the binomial distribution variable with the limiting reactant and constrained firing concepts to avoid negative populations encountered in the original tau-leap method of Gillespie for large time increments, and thus conserve mass. Simulations using prototype reaction networks show that the BD-tau method is more accurate than the original method for comparable coarse-graining in time.

Journal Article↗

Microtubules have special physical associations with smooth endoplasmic reticula and mitochondria in axons.

Ultrastructural morphometry was used to document the non-random spatial distributions of organelles within the compact myelinated region of avian oculomotor axons. These regions contain large numbers of loosely packed neurofilaments (NFs) (241/microns 2) and only a relatively small number of microtubules (MTs) (4/microns 2), mitochondria (0.6/microns 2), and smooth endoplasmic reticulum (SER) (1.6/microns 2). Random co-occurrences between the relatively sparsely distributed MTs, mitochondria, and SER are probably infrequent in these axons. The actual co-occurrences of MTs, mitochondria, and SER with MTs were counted and compared to the co-occurrences expected in a random Poisson distribution. At long distances (200 nm), the co-occurrences were random. At shorter distances (40 nm and less), MTs were still randomly associated with other MTs. However, at these shorter distances, the spatial associations of mitochondria with MTs and of SER with MTs were not random; such preferential stable associations may be produced by specific MT associated cross-bridging proteins. In axons, MTs tend to be clustered together, giving the appearance of MT bundles. We propose that the MT-MT bundling is an indirect result of MT concentration along the continuous intra-axonal SER network, to which the MTs are apparently tied directly by dynamic molecular cross-bridges.

Animals↗

The effect of lethally irradiated cells on the transplantability of murine tumours.

Fully quantitative isogeneic transplantation assays of viable (V) cells of a CBA carcinoma showed that the relationship between log inoculum and frequency of tumour "takes" accorded strictly with a Poisson distribution and indicated that 6900 cells were required for 50% takes (TD50). Addition of 10(5) lethally irradiated (LI) cells of the same tumour to the inocula reduced the TD50 to about 4 cells, yet the Poisson relationship was retained. From this and other data it is concluded that LI cells act by increasing the proportion of viable cells which contribute to tumour initiation; there was no evidence that LI cells affected the rate of proliferation of viable cells. The ability of non-homologous LI cells to reduce the TD50 was widely variable, but LI cells of one allografted tumour were almost as effective as homologous LI cells. Lethally irradiated cells did not assist the "take" of allografted viable tumour cells. Histological comparison revealed no difference of the tissue reaction to inocula of viable and LI cells, and it is questioned whether radiation induced lysis of these latter cells is required for their effect on viable cells. Evidence relating to a hypothesis that viable cells interact with one another as they do with lethally irradiated cells was conflicting.

Air↗